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单次口服大剂量维生素 D₃ 对骨转换标志物的短期影响。

Short-term effects on bone turnover markers of a single high dose of oral vitamin D₃.

机构信息

Rheumatology Unit, Department of Medicine, University of Verona, Policlinico Borgo Roma, Piazzale Scuro, 10, 37134 Verona, Italy.

出版信息

J Clin Endocrinol Metab. 2012 Apr;97(4):E622-6. doi: 10.1210/jc.2011-2448. Epub 2012 Feb 1.

DOI:10.1210/jc.2011-2448
PMID:22298802
Abstract

CONTEXT

Vitamin D deficiency is often treated or prevented by high intermittent doses of vitamin D to achieve a better treatment adherence, but treatment outcomes were contradictory, and even a transient increase in fracture and fall risk was reported.

OBJECTIVE

The objective of the study was to investigate the short-term effects on bone turnover markers of a single bolus of vitamin D₃.

DESIGN, SETTING, PATIENTS, AND INTERVENTION: Twelve elderly subjects (eight women, four men; mean age 76 ± 3 yr) were given a single oral bolus of 600,000 IU vitamin D₃. Blood samples were taken at baseline and 1, 3, 7, 14, 30, 60, and 90 d after vitamin D₃ administration. Twenty-four subjects served as controls.

MAIN OUTCOME MEASURES

Changes in serum levels of 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D, PTH, C-terminal-telopeptides of type I collagen, cross-linked N-telopeptide of type I collagen (sNTX), osteocalcin, and bone-specific alkaline phosphatase.

RESULTS

No relevant changes in 25OHD and bone turnover markers were observed in the controls. In treated subjects, serum 25OHD attained a peak increment to 67.1 ± 17.1 ng/ml (P < 0.001) at d 3. Subsequently it slowly decreased to 35.2 ± 5.8 ng/ml (P <0.01 vs. a baseline value of 21.7 ± 5.6 ng/ml). Mean serum PTH concentration decreased by 25-50% and serum 1,25-dihydroxyvitamin D rose by 25-50%. Serum CTX and sNTX rose significantly at d 1 (P < 0.01), they attained a peak increment greater than 50% at d 3, and they subsequently decreased almost back to baseline values at d 90. Serum osteocalcin slightly rose within the first 3 d and then declined by d 60. No changes were observed in serum bone-specific alkaline phosphatase.

CONCLUSIONS

Our results indicate that the use of large doses of vitamin D may be associated with acute increases in C-terminal-telopeptides of type I collagen and sNTX, which may explain the negative clinical results obtained by using intermittent high doses of vitamin D to treat or prevent vitamin D deficiency.

摘要

背景

维生素 D 缺乏症通常通过大剂量间歇性维生素 D 治疗或预防,以提高治疗依从性,但治疗结果却相互矛盾,甚至有报道称短暂增加骨折和跌倒风险。

目的

本研究旨在探讨单次大剂量维生素 D₃ 对骨转换标志物的短期影响。

设计、环境、患者和干预:12 名老年受试者(8 名女性,4 名男性;平均年龄 76 ± 3 岁)给予口服 600,000IU 维生素 D₃ 单剂量。在维生素 D₃ 给药前和 1、3、7、14、30、60 和 90d 时采集血样。24 名受试者作为对照。

主要观察指标

血清 25-羟维生素 D(25OHD)、1,25-二羟维生素 D、甲状旁腺激素、I 型胶原 C 端肽、I 型胶原交联 N 端肽(sNTX)、骨钙素和骨特异性碱性磷酸酶的变化。

结果

对照组中 25OHD 和骨转换标志物无明显变化。在治疗组中,血清 25OHD 在第 3d 达到 67.1 ± 17.1ng/ml 的峰值增加(P<0.001)。随后,它缓慢下降至 35.2 ± 5.8ng/ml(与基线值 21.7 ± 5.6ng/ml 相比,P<0.01)。平均血清甲状旁腺激素浓度降低 25%-50%,血清 1,25-二羟维生素 D 升高 25%-50%。血清 CTX 和 sNTX 在第 1d 显著升高(P<0.01),在第 3d 达到大于 50%的峰值增加,随后在第 90d 几乎恢复到基线值。血清骨钙素在最初的 3d 内略有升高,然后在第 60d 下降。血清骨特异性碱性磷酸酶无变化。

结论

我们的结果表明,大剂量使用维生素 D 可能与 I 型胶原 C 端肽和 sNTX 的急性增加有关,这可能解释了使用间歇性大剂量维生素 D 治疗或预防维生素 D 缺乏症时获得的负面临床结果。

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